T-Lymphocyte Subset Distribution and Activity in Patients With Glaucoma.

Purpose: Besides glia-driven neuroinflammation, growing evidence from analysis of human blood samples, isolated autoantibodies, and postmortem tissues also support systemic immune responses during neurodegeneration in glaucoma patients. To explore the T-cell-mediated component of systemic immunity, this study analyzed T lymphocytes in patients' blood. Methods: Blood samples were collected from 32 patients with glaucoma and 21 nonglaucomatous controls, and mononuclear cells were isolated by Histopaque density gradient centrifugation. T-cell subset distribution was analyzed by multicolor flow cytometry after helper (Th) and cytotoxic fractions, and Th subpopulations, were stained with antibodies to CD4, CD8, or distinctive markers, such as IFN-γ (for Th1), IL-4 (for Th2), IL-17A (for Th17), and CD25/FoxP3 (for T regulatory cells [Tregs]). In addition, proliferative activity and cytokine secretion of T cells were analyzed after in vitro stimulation. Results: Analysis of T-cell subset distribution detected a glaucoma-related shift. Despite similar frequencies of CD4+ or CD8+ T cells, or Th1, Th2, or Th17 subsets in glaucoma and control groups, glaucomatous samples exhibited a trend toward decreased frequency of CD4+ (or CD8+)/CD25+/FoxP3+ Tregs within the entire CD4+ (or CD8+) population (P < 0.001). Furthermore, CD4+ T cells in glaucomatous samples presented a greater stimulation response (∼3-fold) as characterized by increased proliferation and proinflammatory cytokine secretion (P < 0.05). Conclusions: These findings suggest that the immunity activated in glaucoma may not be counterbalanced by an efficient immune suppression. More work is encouraged to determine whether shifted T-cell homeostasis may contribute to neurodegeneration in glaucoma, and/or whether T-cell subset imbalance may serve as a biomarker of autoimmune susceptibility.

Age-related changes in the peripheral retinal nerve fiber layer thickness.

PURPOSE: This pilot cross-sectional study aimed to determine age-related changes of the retinal nerve fiber layer (RNFL) thickness in retinal periphery by swept-source optical coherence tomography-based analysis. METHODS: Forty eyes of 40 healthy subjects were studied in three age groups, group 1 (20-40 years, n=15), group 2 (41-60 years, n=14), and group 3 (≥61 years, n=11). Wide-angle swept-source optical coherence tomography scans, including the optic disc and macula, were montaged with the nasal peripheral optical coherence tomography images acquired with a contralateral gaze. The peripapillary and peripheral RNFL thickness values were obtained for nasal and temporal sides. The ratio of peripheral-to-peripapillary RNFL thickness was also calculated for these sectors. RESULTS: We detected a significantly thinner RNFL in older than younger subjects at a distance of 6 mm from the optic disc on nasal and temporal sides (P<0.001). An age-related reduction in peripheral-to-peripapillary RNFL thickness ratios (P<0.001 and P<0.02 for nasal and temporal sides, respectively) was also detected. CONCLUSION: The age-related decline should be taken into consideration when determining the glaucoma-related alterations in peripheral RNFL thickness. Continued analysis in patients with ocular hypertension and glaucoma should help determine whether RNFL in the periphery with lower nerve tissue reserve might be more susceptible to injury, whether injury to the peripheral RNFL might be easier to detect, and/or whether analysis of the peripheral RNFL thickness could improve clinical diagnosis and follow-up of glaucoma.

Corneal Sublayers Thickness in Patients With Mitral Valve Prolapse.

OBJECTIVES: The aim of this study was to compare the thickness of each corneal sublayer in patients with mitral valve prolapse (MVP) and healthy individuals. METHODS: A total of 38 eyes from 38 patients with MVP and 34 eyes from 34 age- and sex-matched healthy individuals were included in this study. The thickness of the corneal epithelium, Bowman layer, stroma, and Descemet membrane-endothelium complex were measured on the central cornea (i.e., corneal apex) and both the inferior and superior halves of the cornea with anterior segment module of spectral domain optical coherence tomography. RESULTS: No statistically significant differences emerged between the study and control groups in terms of Bowman layer thickness in the central cornea and the cornea's superior half (P=0.092 and P=0.128, respectively). However, in the inferior half of the cornea, Bowman layer thickness among patients with MVP was 11.95±2.34 µm (range 7-16 µm) and in the control group was 13.03±1.62 µm (range 10-16 µm), which made for a statistically significant difference (P=0.025). CONCLUSIONS: Our study revealed thinning of Bowman layer in the inferior half of the cornea in patients with MVP.

Oxidative Stress-Related Molecular Biomarker Candidates for Glaucoma.

Purpose: Glaucoma-related molecular biomarkers can improve clinical testing to diagnose the disease early, predict its prognosis, and monitor treatment responses. Based on the evidence of increased oxidative stress in glaucomatous tissues, this study analyzed oxidative stress-related biomarker candidates in blood and aqueous humor samples with or without glaucoma. Methods: The blood and aqueous humor samples collected from carefully selected groups of 96 patients with glaucoma and 64 healthy subjects without glaucoma were included in the study. The samples were analyzed for protein carbonyls and advanced glycation end products (AGEs) through ELISA-based quantification assays. To allow proper comparisons, the Goldmann-Witmer coefficient that reflects the ratio of aqueous humor to blood values corrected to total protein concentration in individual samples was calculated. Results: Blood and aqueous humor levels of protein carbonyls and AGEs were found significantly higher in glaucomatous samples compared with age-matched nonglaucomatous controls (P < 0.001). The glaucoma-related increase in protein carbonyls and AGEs was more prominent in aqueous humor samples than blood samples (2.6-fold versus 1.9-fold for protein carbonyls, and 3.1-fold versus 1.9-fold for AGEs; P < 0.001). Comparison of the Goldmann-Witmer coefficients indicated greater values for protein carbonyls (1.37 ± 0.3 vs. 3.07 ± 0.8) and AGEs (1.2 ± 0.3 vs. 3.2 ± 1.1) in the glaucoma group (P < 0.001). Conclusions: Findings of this study encourage further validation studies of oxidative stress-related biomarkers in glaucoma. Analysis of protein carbonyls and AGEs in longitudinal studies of larger and heterogeneous patient cohorts should better assess the value of these promising candidates as molecular biomarkers of glaucoma for clinical predictions.

Evaluation of foveal photoreceptor layer in eyes with macular edema associated with branch retinal vein occlusion after ozurdex treatment.

The aim of this study was to evaluate the central retinal thickness (CRT), outer nuclear layer thickness (ONLT), photoreceptor layer thickness (PLT), photoreceptor layer integrity, and the correlation between visual acuity and PLT in eyes with branch retinal vein occlusion (BRVO) 2 months after treatment with intravitreal dexamethasone implant (Ozurdex; Allergan, Inc, Irvine, CA). In this prospective study, 32 eyes of 32 patients were enrolled. A single injection of Ozurdex was administered to all the patients. CRT, ONLT, and PLT were measured using spectral-domain optical coherence tomography before and 2 months after the injection. Best-corrected visual acuity (BCVA [logMAR]) and photoreceptor cell integrity were also evaluated. The average CRT, ONLT, PLT, and BCVA values for the sample group before the treatment were as follows: 707 ± 261, 608 ± 288, 70 ± 25, and 0.96 ± 0.22 µm, respectively. The average CRT, ONLT, PLT, and BCVA values for the sample group 2 months after the Ozurdex injection were as follows: 299 ± 149, 211 ± 138, 77 ± 20, and 0.63 ± 0.30 µm, respectively (p < 0.05). Two months after the Ozurdex injection, BCVA correlated with ONLT and PLT (r = 0.365, p = 0.048 and r = -0.488, p = 0.021, respectively), whereas BCVA was not correlated with CRT (r = 0.239, p = 0.189). Photoreceptor layer is associated with the visual function of eyes with macular edema secondary to BRVO. Also, ONLT seems to be more closely related to visual acuity improvement than CRT decrement.

Accelerated corneal crosslinking for treatment of progressive keratoconus in pediatric patients.

PURPOSE: To evaluate the safety and efficacy of accelerated corneal crosslinking (CXL) in patients with progressive keratoconus aged 18 years or less. METHODS: A total of 28 eyes from 19 patients with progressive keratoconus aged 18 years or less were enrolled. We divided participants into 2 groups according to corneal thickness (CT). Group 1 included 13 eyes of 8 patients with CT ≥450 µm; group 2 included 15 eyes of 11 patients with CT <450 µm. Each participant underwent accelerated CXL using 10-minute ultraviolet A irradiance at 9 mW/cm2 for a total energy dose of 5.4 J/cm2. The efficacy and safety of the procedure were assessed postoperatively at 1, 3, 6, and 12 months with Pentacam and visual acuity. RESULTS: In uncorrected visual acuity, group 1 showed a statistically significant +0.12 logMAR improvement at 3 months postoperatively (p = 0.003), and in group 2, there was a statistically significant +0.3 logMAR improvement at 1 month postoperatively (p = 0.005). In best-corrected visual acuity, there was a +0.15 logMAR (p<0.001) and +0.22 logMAR (p = 0.005) improvement in group 1 and group 2, respectively, at 12 months postoperatively. All mean keratometric values including K1 and K2 dropped by at least 1 D or remained stable (< ± 1 D) in both groups after accelerated CXL treatment. CONCLUSIONS: The findings showed that accelerated CXL treatment seems to be effective in slowing or halting the progression of keratoconus and that no permanent apparent complications are noted 6 months after accelerated CXL.

Evaluation of anterior segment parameters in patients with neurofibromatosis type 1.

PURPOSE: To evaluate anterior segment parameters in patients with neurofibromatosis type 1 (NF1) in comparison to healthy individuals. METHODS: A total of 34 eyes from 17 patients with NF1 and 34 eyes from 17 age- and sex-matched healthy individuals were included in this study. Each participant underwent a comprehensive ophthalmic assessment including best-corrected visual acuity, slit-lamp biomicroscopy, stereoscopic fundus examination, and intraocular pressure. Central corneal thickness, corneal volume, corneal curvatures (K1 and K2), anterior chamber depth, anterior chamber volume, iridocorneal angle, and pupil size values were measured by Pentacam Scheimpflug camera. RESULTS: The mean anterior chamber depth, iridocorneal angle, and anterior chamber volume measurements revealed significantly lower values when compared with the control group (p<0.001, p<0.001, and p = 0.041, respectively). However, the mean pupil size was significantly larger when compared with the control group (p = 0.008). Central corneal thickness, corneal volume, K1, and K2 values were similar between the study and control groups (p = 0.875, p = 0.549, p = 0.066, and p = 0.166, respectively). CONCLUSIONS: Our results reveal that NF1 is associated with statistically significant alterations in anterior chamber depth, iridocorneal angle, anterior chamber volume, and pupil size in patients with NF1 when compared with healthy controls.

The Impact of Reused Phaco Tip on Outcomes of Phacoemulsification Surgery.

PURPOSE: To evaluate the impact of reused phaco tip on intraoperative performance and postoperative outcomes after 2.2 mm micro-coaxial torsional and transversal phacoemulsification. MATERIAL AND METHODS: This prospective randomized study enrolled 136 eyes of 136 cataract patients; 68 eyes in torsional group (34 eyes with single use tip, 34 eyes with reused tip) and 68 eyes in transversal group (34 eyes with single use tip, 34 eyes with reused tip). Intraoperative measurements were total ultrasound (U/S) time, torsional U/S time, cumulative dissipated energy (CDE), estimated fluid use (EFU) in the torsional group and total phacoemulsification time (TPT), and effective phacoemulsification time (EPT) in transversal phacoemulsification. The central endothelial cell density (ECD) and the central corneal thickness (CCT) were evaluated preoperatively and postoperatively at 1 and 30 days using noncontact specular microscopy. RESULTS: Intraoperative measurements in torsional phacoemulsification showed significant increase in total U/S time (p = 0.01), torsional U/S time (p = 0.01), and CDE (p = 0.01) with the reused tip. The EFU was similar in both tip groups (p = 0.36). The total U/S time, torsional U/S time, and CDE in torsional group were significantly increased with the reused tip for grade III (p = 0.03 for all parameters) and grade IV cataracts (p = 0.005 for torsional U/S time and CDE; p = 0.006 for total U/S time). Intraoperative measurements in transversal phacoemulsification showed no differences in TPT and EPT between tip groups (p > 0.05). The change in ECD and CCT in torsional and transversal phacoemulsification groups were similar in both tip groups (p > 0.05). CONCLUSIONS: This study showed that sharpness of phaco tip edge increases the efficiency of torsional phacoemulsification for hard cataracts. This result does not mean that reused phaco tip may be used in soft and medium cataracts. As the timing of tip's change is a user-dependent procedure, a new single phaco tip should be used in each case if possible.

Comparison of 45-degree Kelman and 45-degree balanced phaco tip designs in torsional microcoaxial phacoemulsification.

AIM: To compare the intraoperative performance and postoperative outcome after microcoaxial torsional phacoemulsification using either a Kelman or balanced phaco tip. METHODS: Cataracts were treated using 2.2 mm microcoaxial torsional phacoemulsification using either a 45-degree mini-flared Kelman(®) or a 45-degree Intrepid(®) Balanced phaco tip. Intraoperative measurements included total ultrasound (US) time, cumulative dissipated energy (CDE), torsional US time, and balanced salt solution (BSS) use. The central endothelial cell density (ECD) and central corneal thickness (CCT) were evaluated preoperatively and postoperatively 1, 7, and 30d after surgery using noncontact specular microscopy. RESULTS: The 116 enrolled eyes (116 patients) were divided equally between the Kelman and balanced tip groups. Intraoperative measurements showed significantly less total US time, torsional US time, CDE, and BSS use in the balanced group than in Kelman group (P<0.05). The total US time, torsional US time, CDE, and BSS use were 17.45±14.53s, 16.63±13.97s, 6.38±5.26, and 48.21±17.21 mL in the Kelman group and 11.39 ± 9.60s, 10.90 ± 9.25s, 4.04 ± 3.42, and 41.36 ± 12.70 mL in the balanced group, respectively. CONCLUSION: Torsional phacoemulsification performed with a balanced tip provided more effective lens removal with less total US time, torsional time, CDE, and BSS use, as well as similar changes in ECD with a Kelman tip in all cataract grades. This special designed phaco tip for torsional phacoemulsification provides an alternative phaco tip for many surgeons' preference with straight phaco tip.